Immune cell localization in different compartments of human end-stage cystic fibrosis lungs

Abstract

Introduction: CF is characterized by chronic inflammation of the lungs; however the extent and localization of innate & adaptive immune cells has insufficiently been established.

Objectives: To perform quantitative immunohistochemical analyses in lung tissue from CF patients and healthy controls (HC) & localize cells to airways, blood vessels (BV) or parenchyma.

Methods: 8µm sections of lung biopsies of CF patients taken during transplantation (n=20) & HC lung biopsies (n=22) were stained for Th cells (CD4), mast cells (MC)(tryptase), eosinophils (EG2) & dendritic cells (DC)(CD1a&CD207; langerin). Quantification was performed by counting number of cells over total area (mm²) of biopsy (Th cells) or in 10 high power fields averaged per compartment (airways, BV & parenchyma) per subject (MC, eosinophils & DC).

Results: CD4⁺ T cell counts were significantly increased in CF vs. HC (p=0.001) and were present as dispersed single cells (CF&HC) or organized in follicles mainly situated in parenchyma (mostly CF). Both total & compartmental MC & DC counts were significantly increased in CF vs. HC (all p<0.001) whereas eosinophil counts showed no difference. MC, DC & eosinophil counts were higher around airways than around BV or parenchyma. Female CF patients (n=10) had significantly higher Th cell, MC, Langerhans-type DC & eosinophil counts than males (all p<0.03).

Conclusion: There is increased presence of Th cells, MC & DC in the end-stage CF lung, albeit in different compartments. Inflammation was more severe in female CF patients irrespective of FEV₁, colonization status or genotype, corroborating previous data suggesting a direct deleterious effect of female hormone on inflammation in the CF lung.